Every cell of an organism contains genomic DNA that keeps encoded information about all proteins of all cells of the organism and eventually about the whole organism and its development. Initially this genomic DNA is identical in all cells of an organism. But as the organism grows genomic DNA of every cell becomes subjected to mutational pressure due to environmental factors and mistakes of cellular replication and repair machinery. The known cellular DNA repair mechanisms replace damaged or incorrect DNA bases and rejoin ends of DNA after single-strand and double-strand breaks immediately after mutational events. They can also employ the second DNA chain as a template. When the damage is rather long and affects both DNA chains its repair becomes problematic and the damage results in mutation. The double-strand break repair mechanism can itself be a source of mutations (Pfeifer, P., The mutagenic potential of DNA double-strand break repair. 1998, 96–97, 119–129). As mutations are accumulated in the cellular genome they can cause malfunction of some cells or cancerous transformation.
Environmental mutagenic factors and errors of cellular replication and repair are sources of somatic cell mutations. It has been suggested that gradual accumulation of mutations in cells can cause multi-step cancer transformation. Somatic mutations are considered to be the main cause of aging. Mutations may also induce development of some hereditary associated diseases such as cardio-vascular diseases, high blood pressure, rheumatoid arthritis, and diabetes.
The genetic, multi-mutational nature of cellular cancer transformation and cancer itself suggests that methods of cancer therapy should be directed to the cause of the disease and particularly targeted to the treatment of mutations. Methods for fixing definite point mutations in cells have been suggested (U.S. Pat. No. 5,795,972 issued to Kmiec on Aug. 18, 1998, which is incorporated herein by reference) but according to the method, mutations must be precisely identified before each treatment. Because not a single mutation has been 100% proven to cause a cancer, the development of these methods requires additional fine and time-consuming research. There is a need for methods which can be applied based upon the current knowledge underlying the causes of cancer.
Applying DNA fragments locally has been suggested for treatment of precancerous conditions in skin of patients and for tanning stimulation (U.S. Pat. No. 5,955,059 issued to Gilchrest, et al., on Sep. 21, 1999; and U.S. Pat. No. 5,470,577 issued to Gilchrest, et al., Nov. 28, 1995, both of which are incorporated herein by reference). No sequences or sources of DNA are specified. Rather, the patent suggests that ‘any appropriate sources’ DNA natural or synthetic, for example, salmon DNA with the length from 200 to mononucleotides and nucleosides including dimers, the most potent agents in their tests can be used.
Another method to activate DNA repair in cells is offered including delivery of enzymes participating in DNA repair into skin cells (U.S. Pat. No. 5,352,458 issued to Yarosh, Oct. 4, 1994; and U.S. Pat. No. 5,302,389 issued to Kripke, et. al., Apr. 12, 1994, both of which are incorporated herein by reference). However the latter methods do not suggest fixing of already established or inherited mutations.
There remains a need for methods of correcting genetic mutations. There remains a need for treating individuals who have diseases and disorders associated with genetic mutations. There remains a need to replace undesirable alleles with desirable alleles. There is a further need for methods for inducing tolerance to prevent transplant rejection. There is a further need for methods for inducing tolerance to treat and prevent allergies. There is a need for methods for increasing fertility.